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Trichothiodystrophy due to ERCC2 Variants: Uncommon Contributor to Progressive Hypomyelinating Leukodystrophy
Ali Reza Tavasoli1,2, Arastoo Kaki3,4, Maedeh Ganji5
1Neurology Division, Barrow Neurological Institute, Phoenix Children's, Phoenix, Arizona, USA.
Molecular Genetics & Genomic Medicine
|February 20, 2025
Summary
Trichothiodystrophy (TTD) linked to ERCC2 gene variants can cause progressive hypomyelination. This study identifies novel ERCC2 variants associated with hypomyelinating leukodystrophy in TTD patients.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Trichothiodystrophy (TTD) is a rare genetic disorder.
- It is caused by variants in DNA repair genes, including ERCC2.
- Cerebral white matter abnormalities are known in TTD, but myelination disorders are uncommon.
Purpose of the Study:
- Investigate the genetic basis of TTD with progressive hypomyelination.
- Characterize the phenotype associated with novel ERCC2 variants.
- Contribute to understanding ERCC2-related leukodystrophies.
Main Methods:
- Autism/ID gene Panel sequencing in a pediatric patient.
- Serial brain imaging over 5 years.
- Comprehensive literature review of ERCC2 variants and myelination disorders.
Main Results:
- Identified compound heterozygous ERCC2 variants (c.2190+1delG and c.1479+2dupT) causing TTD.
- Patient presented with microcephaly, failure to thrive, and developmental delay.
- This is the first report of hypomyelinating leukodystrophy in TTD patients with these ERCC2 variants.
Conclusions:
- ERCC2 variants are implicated in hypomyelinating leukodystrophy within TTD.
- This finding expands the phenotypic spectrum of ERCC2-related disorders.
- Highlights the importance of genetic testing for diagnosing rare neurological conditions.
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